Patients with stricturing or penetrating Crohn\u27s disease phenotypes report high disease burden and treatment needs

BACKGROUND: Crohn\u27s disease (CD) is a chronic autoimmune disease in which inflammation can progress to complications of stricturing and/or penetrating disease. Real-world data on burden of complicated CD phenotypes are limited. METHODS: We analyzed cross-sectional data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry from 2016 to 2020. Four mutually exclusive phenotype cohorts were created: inflammatory CD (CD-I), complicated CD (stricturing CD, penetrating CD, and stricturing and penetrating CD [CD-SP]). Statistical analyses were performed using CD-I as the reference. RESULTS: A total of 1557 patients were identified: CD-I (n = 674, 43.3%), stricturing CD (n = 457, 29.4%), penetrating CD (n = 166, 10.7%), and CD-SP (n = 260, 16.7%). Patients with complicated phenotypes reported significantly greater use of tumor necrosis factor inhibitors (84.2%-86.7% vs 66.0%; P \u3c .001) and corticosteroids (75.3%-82.7% vs 68.0%; P \u3c .001). Patients with CD-SP reported significantly more aphthous ulcer (15.4% vs 10.5%; P \u3c .05), erythema nodosum (6.5% vs 3.6%; P \u3c .05), inflammatory bowel disease-related arthropathy (25.8% vs 17.2%; P \u3c .01), liquid stools (24.2% vs 9.3%; P \u3c .001), nocturnal fecal incontinence (10.8% vs 2.5%; P \u3c .001), and CD-related surgery (77.7% vs 12.2%; P \u3c .001). CONCLUSIONS: Patients with complicated CD phenotypes reported higher rates of active CD-related luminal and extraintestinal manifestations, and underwent more surgeries, despite being more likely to have received biologics than those with CD-I. The potential for early recognition and management of CD-I to prevent progression to complicated phenotypes should be explored in longitudinal studies

Disease burden of urinary tract infections among type 2 diabetes mellitus patients in the U.S.

AbstractAimsType 2 diabetes is a reported risk factor for more frequent and severe urinary tract infections (UTI). We sought to quantify the annual healthcare cost burden of UTI in type 2 diabetic patients.MethodsAdult patients diagnosed with type 2 diabetes were identified in MarketScan administrative claims data. UTI occurrence and costs were assessed during a 1-year period. We examined UTI-related visit and antibiotic costs among patients diagnosed with UTI, comparing those with versus without a history of UTI in the previous year (prevalent vs. incident UTI cases). We estimated the total incremental cost of UTI by comparing all-cause healthcare costs in patients with versus without UTI, using propensity score-matched samples.ResultsWithin the year, 8.2% (6,014/73,151) of subjects had ≥1 UTI, of whom 33.8% had a history of UTI. UTI-related costs among prevalent versus incident cases were, respectively, $603 versus$447 (p=0.033) for outpatient services, $1,607 versus$1,819 (p=NS) for hospitalizations, and $61 versus$35 (p<0.0001) for antibiotics. UTI was associated with a total all-cause incremental cost of $7,045 (95% CI: 4,130, 13,051) per patient with UTI per year.ConclusionsUTI is common and may impose a substantial direct medical cost burden among patients with type 2 diabetes

Assessing the Impact of Propensity Score Estimation and Implementation on Covariate Balance and Confounding Control Within and Across Important Subgroups in Comparative Effectiveness Research

Researchers are often interested in estimating treatment effects in subgroups controlling for confounding based on a propensity score (PS) estimated in the overall study population

Predictive Modeling of Hypoglycemia for Clinical Decision Support in Evaluating Outpatients with Diabetes Mellitus

Objective: Hypoglycemia occurs in 20–60% of patients with diabetes mellitus. Identifying at-risk patients can facilitate interventions to lower risk. We sought to develop a hypoglycemia prediction model. Methods: In this retrospective cohort study, urban adults prescribed a diabetes drug between 2004 and 2013 were identified. Demographic and clinical data were extracted from an electronic medical record (EMR). Laboratory tests, diagnostic codes and natural language processing (NLP) identified hypoglycemia. We compared multiple logistic regression, classification and regression trees (CART), and random forest. Models were evaluated on an independent test set or through cross-validation. Results: The 38,780 patients had mean age 57 years; 56% were female, 40% African-American and 39% uninsured. Hypoglycemia occurred in 8128 (539 identified only by NLP). In logistic regression, factors positively associated with hypoglycemia included infection, non-long-acting insulin, dementia and recent hypoglycemia. Negatively associated factors included long-acting insulin plus sulfonylurea, and age 75 or older. The models’ area under curve was similar (logistic regression, 89%; CART, 88%; random forest, 90%, with ten-fold cross-validation). Conclusions: NLP improved identification of hypoglycemia. Non-long-acting insulin was an important risk factor. Decreased risk with age may reflect treatment or diminished awareness of hypoglycemia. More complex models did not improve prediction

Reliability and Feasibility of Methods to Quantitatively Assess Peripheral Edema

Objective: To evaluate methods to assess peripheral edema for reliability, feasibility and correlation with the classic clinical assessment of pitting edema

Assessing the Impact of Propensity Score Estimation and Implementation on Covariate Balance and Confounding Control Within and Across Important Subgroups in Comparative Effectiveness Research

PURPOSE: Researchers are often interested in estimating treatment effects in subgroups controlling for confounding based on a propensity score (PS) estimated in the overall study population. OBJECTIVE: To evaluate covariate balance and confounding control in sulfonylurea (SU) versus metformin (MET) initiators within subgroups defined by cardiovascular disease history (CVD) comparing an overall PS with subgroup-specific PSs implemented by 1:1 matching and stratification. METHODS: We analyzed younger patients from a US insurance claims database and older patients from two Medicare (Humana Medicare Advantage, fee-for-service Medicare Parts A, B and D) datasets. Confounders and risk factors for acute myocardial infarction (AMI) were included in an overall PS and subgroup PSs with and without CVD. Covariate balance was assessed using the average standardized absolute mean difference (ASAMD). RESULTS: Compared to crude estimates, ASAMD across covariates was improved 70–94% for stratification for Medicare cohorts and 44–99% for the younger cohort, with minimal differences between overall and subgroup-specific PSs. With matching, 75–99% balance improvement was achieved regardless of cohort and PS, but with smaller sample size. Hazard Ratios within each CVD subgroup differed minimally among PS and cohorts. CONCLUSION: Both overall PSs and CVD subgroup-specific PSs achieved good balance on measured covariates when assessing the relative association of diabetes monotherapy with nonfatal MI. PS matching generally led to better balance than stratification, but with smaller sample size. Our study is limited insofar as crude differences were minimal, suggesting that the new user, active comparator design identified patients with some equipoise between treatments

Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum : A blueprint for clinical trial design

Background Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes. Methods and results Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF. Conclusion HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk

Postprandial metabolic responses to mixed versus liquid meal tests in healthy men and men with type 2 diabetes

AbstractAimsCompare metabolic responses after mixed versus liquid meals of similar caloric/nutritional content in healthy and type 2 diabetes (T2D) subjects.MethodsTen healthy men and 10 men with T2D received mixed and liquid meals after an overnight fast. Classical (insulinogenic index; insulin/glucose areas under curves, AUCinsulin/AUCglucose) and model-based (beta-cell glucose sensitivity; rate sensitivity; potentiation factor ratio, PFR) beta-cell function estimates were calculated. Between-meal differences in glucose, insulin, C-peptide, triglyceride (TG), beta-cell function and oral glucose insulin sensitivity (OGIS) and between-meal correlations for beta-cell function and OGIS were evaluated.ResultsAmong healthy subjects, beta-cell function and OGIS were similar between meals. C-peptide (p=0.03), insulin (p=0.002), AUCinsulin/AUCglucose (p=0.004) and insulin secretion (p=0.04) were higher after the liquid meal. Among T2D subjects, glucose, insulin, C-peptide, beta-cell function, and OGIS were similar. PFR was higher (p=0.004) and TG increased more slowly (p=0.002) after the liquid meal. OGIS and beta-cell function were correlated during both meals in both groups (r=0.66–0.98), except incremental AUCinsulin/AUCglucose, rate sensitivity, and, in healthy subjects, PFR.ConclusionsMetabolic responses after mixed or liquid meals of similar content were highly correlated in T2D and healthy subjects. In T2D, the liquid meal produced beta-cell function estimates generally similar to the mixed meal